Feasibility, Oligometastatic Disease, Personalized Medicine
Conditions
Brief summary
This is a feasibility trial to assess use of OncoTarget and OncoTreat testing in a basket design of patients with oligmetastasis across various solid tumor histology. Eligible oligometastatic patients that are receiving radiation therapy (n=20) will undergo mandatory tumor biopsy prior to precision medicine testing. Formalin fixed paraffin embedded tissue with \>50% tumor will be sent to the Laboratory of Personalized Genomic Medicine at Columbia University Medical Center for Darwin OncoTarget and OncoTreat testing. This will be supplementing routine clinical care with the goal of improving outcomes. The treating oncologist will decide to administer standard of care systemic therapy or proceed with treatment recommended by precision medicine testing. Feasibility outcomes include the ability to have the OncoTarget and OncoTreat test performed based on tumor type and pathology, ability to procure agents, change in medication use, and identification of unknown barriers. This study is assessing the use of precision medicine in a population has documented poor outcomes with implications aimed at improving these outcomes.
Detailed description
Despite significant progress in solid tumor oncology, including widespread genomic testing, metastatic cancer remains largely incurable and results in approximately 90% of cancer deaths. In the context of systems biology, RNA transcriptome-based (RNA-seq) testing is utilized to identify master regulator proteins that are putative drivers of tumor progression. After extensive preclinical testing and validation, Darwin OncoTarget and OncoTreat has been developed as a commercially available next generation precision oncology test with preliminary evidence of efficacy in treatment-refractory advanced cancers. We designed this pilot trial to assess the feasibility of integrating Darwin OncoTarget and OncoTreat testing in patients with oligometastases receiving comprehensive involved site radiotherapy. Eligible patients are adults with solid tumor oligometastases with up to 10 discrete tumors amenable to radiation therapy following prior first-line systemic therapy. Tumor biopsy is required to allow for precision medicine testing to supplement standard clinical management. Formalin fixed paraffin embedded tissue with \>50% tumor will be sent to the Laboratory of Personalized Genomic Medicine at Columbia University Medical Center for Darwin OncoTarget and OncoTreat testing. Patients will either continue standard of care systemic therapy or proceed with an alternative FDA approved treatment informed by Darwin testing. This trial evaluates the feasibility and utility of integrating novel precision oncology testing in a community hospital setting. This study will utilize precision oncology testing in the population of induced, recurrent or persistent oligometastases that currently have limited or largely ineffective systemic treatment options. This trial represents an early attempt at integrating next generation precision medicine testing and systems biology in the context of radiation therapy.
Interventions
DIAGNOSTIC_TESTDarwin OncoTarget and OncoTreat
Darwin OncoTarget and OncoTreat predict potential drugs with early markers of efficacy in early human clinical trials. Specifically, OncoTarget identifies high-affinity inhibitors of master regulator proteins, while OncoTreat identifies tumor-checkpoint module inhibitors that modulate the transcriptional activity of hyper-connected master regulators. These tests are now commercially available with Clinical Laboratory Improvement Amendments (CLIA) approval through Columbia Presbyterian Medical Center.
Sponsors
Good Samaritan Hospital Medical Center, New York
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Feasibility of n=20
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients age ≥18 years with metastatic solid tumor who are candidates for comprehensive involved site radiotherapy to all areas of disease seen on whole body imaging. * Patients with brain metastases are eligible provided they qualify as oligometastases (up to 10 lesions based on the SABR-COMET-10 trial) and are treatable with radiotherapy to all areas of visible disease. * Patients with adequate bone marrow (absolute neutrophil ≥1000, hemoglobin ≥ 9 g/dl, platelets ≥100,000), kidney (creatinine ≤1.5 times upper limit of normal) and liver (bilirubin ≤1.5 times upper limit of normal). * Patients being treated by radiation oncology at Good Samaritan University Hospital.
Exclusion criteria
* Patients with an estimated median survival of less than 6 months using the published and validated NEAT methodology. * Patients who are pregnant and/or breast feeding or those with severe uncontrolled cardiac, pulmonary, infectious or organic brain disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility: Test Performance Ability To Perform Test Versus Unable to Perform Test with Pathology Samples Needed >50% Tumor Tissue | Through study completion, an average of 2 years | Proportion of participants whose tumor biopsy successfully undergoes OncoTarget and OncoTreat testing based on sufficient cellularity/DNA/RNA, defined as \>50% tumor. |
| Feasibility: Percent Medication Change Versus No Medication Change Based on Treating Medical Oncologist Decision | Through study completion, an average of 2 years | Percentage of participants whose chemotherapy management plan is changed based on the willingness of the medical oncologist to try at least one off-label medication recommended by Darwin testing. |
| Feasibility: Percent Medication Procured Through Insurance and/or Compassionate Use Versus Unable to Attain | Through study completion, an average of 2 years | Out of the participants who are prescribed a drug from Darwin testing, the percentage that are procured FDA approved on-label and/or off-label agents through insurance or compassionate use in the setting of extensive preauthorization requirements prevalent in community oncology practice. |
| Feasibility: Qualitative Measurement of Barriers Noted Throughout Study | Through study completion, an average of 2 years | Quantification and explanation of any unknown barriers that occur throughout the study process preventing an eligible participant from starting a drug recommended by Darwin testing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Therapy Change Compared to Standard of Care | Through study completion, an average of 2 years | The proportion of cases where OncoTarget and OncoTreat testing, compared to standard of care genomic testing including Foundation One or Caris, results in a change in systemic treatment that can be implemented in a community hospital setting. |
| Progression-Free Survival | Patients will be followed as per standard of care, up to 5 years or until death. Event determined from date of enrollment until first documented progression or death from any cause, whichever came first, assessed up to 5 years. | Progression-free survival defined as the time between enrollment and tumor progression or death for patients with oligometastases treated with comprehensive involved site radiotherapy compared to historical control patients treated without OncoTarget and OncoTreat testing. |
Countries
United States
Outcome results
None listed